Multiple system atrophy is a progressive neurodegenerative condition caused by cell loss and alpha-synuclein inclusions in the basal ganglia, brain stem, and/or cerebellum. The average age of onset is 50-55 years. Autonomic dysfunction almost always develops during the course of the disease and can include orthostatic hypotension, erectile dysfunction, urinary incontinence, constipation, or supine hypertension.

Some patients may present with predominantly parkinsonian symptoms including bradykinesia, rigidity, tremor, and/or postural instability (parkinsonian type multiple system atrophy [MSA-P]). Others present with predominantly cerebellar signs including ataxia, dysarthria, and oculomotor abnormalities (cerebellar type MSA [MSA-C]). There may also be hyperreflexia, extensor plantar responses, myoclonus, orofacial dystonia, rapid eye movement (REM)-sleep behavior disorder, respiratory stridor, dysphagia, emotional incontinence, Raynaud phenomenon (cold hands / feet), anterocollis, and contractures. Early onset of falling is common. Cognition remains relatively intact.

There is usually a poor or unsustained response to levodopa. Rapid progression is common and prognosis is poor; death typically occurs within 10 years of symptom onset.